Fixed Dose Combinations (FDCs)
of Drugs

R.K. Rishi

Introduction
Fixed dose combinations (FDCs) of drugs are important
for public health perspective and commonly used for the
treatment of pain & inflammation, hypertension,
diabetes, malaria, tuberculosis, HIV/AIDs etc. These
ailments are considered to be the foremost threats to
health in the world today. FDCs have proved to be
advantageous as they are safe and effective. They
increase efficiency, reduce the incidence of adverse
drug effects, and improve patient compliance. The FDCs
offer low cost as compared to individual components of
active ingredients. On other hand if administered in
unprofessional way, FDCs have given problem of drug
resistance in the case of antimicrobial treatment
especially in case of treatment of tuberculosis malaria.
In some instances wrong understanding of FDCs have been
proved to be fatal.Advantages & disadvantages of FDC’s
FDCs offer simple dosage schedule which improves patient
compliance and therefore improves treatment outcomes.
This is especially important in elderly patients or
patients suffering from multiple disorders. The FDCs are
more economic than single ingredient drugs. Such reduced
"pill burden" can greatly enhance the overall treatment
outcome. However, FDCs have certain disadvantages.
Multiple ingredients in an FDC can confuse the physician
who may not remember the exact composition and dose of
individual active ingredient in a particular FDC. The
patient may not actually need all the drugs present in
the combination. That may lead to therapeutic confusion
of therapeutic aims and create false sense of
superiority of two drugs over one especially in case of
antimicrobials and painkillers. If one drug is
contraindicated for a patient, whole FDC cannot be
prescribed. In case of FDCs, dosing is inflexible and
cannot be regulated to patient’s needs (each patient has
unique characteristics such as weight, age,
pharmacogenetics, co-morbidity, which may alter drug
metabolism and effect).Approval of FDCs in India
FDC in India is treated as new drug as per the Rule 122
E of Drugs and Cosmetics Rules. This is because of the
fact that that by combining two or more drugs, the
safety, efficacy, and bioavailability of the individual
Active Pharmaceutical Ingredient (API) may change. DCGI
is the licensing authority notified under section 21(b)
of Drugs and Cosmetics Act. The rationality of an FDC is
examined in the office of DCGI as per the provisions of
Schedule Y before its market authorization in the
country. The applicant pharmaceutical company is
required to submit exhaustive information justifying the
rationale of the FDC in question. The examination
process also involves external experts in their relevant
field including pharmacologists. The safety and efficacy
of the FDC is later ascertained by conducting clinical
trial and bioequivalence studies. Once the data from
clinical studies has been found satisfactory by the DCGI,
permission to manufacture and market the FDC is granted.
It is pertinent to note that recently DCG(I) office has
made guidelines for submission of proposals for FDCs for
the purpose of market authorization in the country.
These guidelines are quite exhaustive and can be
accessed at
www.cdsco.nic.in